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The Spine Journal : Official Journal of... Jun 2024Current protocols on cervical immobilization post-cervical spine fracture are widely accepted in the acute rehabilitation of older adults, however consensus on its... (Review)
Review
BACKGROUND
Current protocols on cervical immobilization post-cervical spine fracture are widely accepted in the acute rehabilitation of older adults, however consensus on its overall effectiveness remains lacking.
PURPOSE
Summarize information from original studies on available cervical immobilization protocols following a cervical fracture and to answer the questions; Which types of study designs have been used to assess the effectiveness of these protocols? What are the currently reported cervical immobilization protocols following cervical fracture in adults? What is the effectiveness of these protocols? What adverse events are associated with these protocols?
STUDY DESIGN
Scoping review was performed PATIENT SAMPLE: Searches were performed on the following online databases from inception to February 23, 2023: EMBASE, MEDLINE, CINAHL, and CENTRAL. Databases were searched for articles pertaining to collar use post cervical spine fracture.
OUTCOME MEASURES
Effectiveness of the cervical fracture immobilization protocols was the primary outcome, examined by various measures including union rates and disability indexes.
METHODS
4 databases were searched; EMBASE, MEDLINE, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL) beginning on February 23, 2023, where 5,127 studies were yielded and 32 were extracted based on studies of adults (≥18 years) with a diagnosis of a cervical fracture (C0-C7) managed with a rigid external orthosis to prevent instability and surgery (collar, or cervicothoracic orthosis). Risk of bias was assessed using the guidelines set out by the Joanna Briggs Institute.
RESULTS
This scoping review yielded low-level prospective (18%) and retrospective (69%) cohort studies, case-control studies (3%), and case series (6%) from 1987 to 2022, patient age ranged from 14 to 104 years. Findings were difficult to summarize based on the lack of randomized controlled trials, leading to no clear conclusions drawn on the presence of standardized cervical immobilization protocols with no information on the duration of treatment or transition in care. Most included articles were retrospective cohort studies of poor to moderate quality, which have significant risk of bias for intervention questions. The effectiveness of these protocols remains unclear as most studies evaluated heterogeneous outcomes and did not present between-group differences. Mortality, musculoskeletal (MSK) complications, and delayed surgery were common adverse events associated with cervical collar use.
CONCLUSION
This scoping review highlights the need for higher levels of evidence as there is currently no standardized immobilization protocol for cervical spine fractures as a primary treatment, the effectiveness of cervical immobilization protocols is unclear, and mortality, MSK complications, and delayed surgery are common adverse events. No sources of funding were used for this scoping review.
PubMed: 38908439
DOI: 10.1016/j.spinee.2024.05.012 -
The Journal of Nutrition, Health & Aging Jun 2024An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate...
BACKGROUND
An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community.
METHODS
Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs).
RESULTS
1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used.
CONCLUSIONS
Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults.
PubMed: 38908297
DOI: 10.1016/j.jnha.2024.100290 -
Biological Research Jun 2024Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor...
BACKGROUND
Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention.
RESULTS
Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not.
CONCLUSION
PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD.
Topics: Fetal Alcohol Spectrum Disorders; Animals; Disease Models, Animal; Physical Conditioning, Animal; Female; Muscle Strength; Pregnancy; Male; Rats; Prenatal Exposure Delayed Effects; Rats, Wistar
PubMed: 38907274
DOI: 10.1186/s40659-024-00520-2 -
Reproductive Biology and Endocrinology... Jun 2024Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian...
BACKGROUND
Premutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, defined as between 55 and 200 CGGs, have been implicated in fragile X-associated primary ovarian insufficiency (FXPOI). Only 20% of female premutation carriers develop early ovulatory dysfunction, the reason for this incomplete penetrance is unknown. This study validated the mathematical model in premutation alleles, after assigning each allele a score representing allelic complexity. Subsequently, allelic scores were used to investigate the impact of allele complexity on age at amenorrhea for 58 premutation cases (116 alleles) previously published.
METHODS
The allelic score was determined using a formula previously described by our group. The impact of each allelic score on age at amenorrhea was analyzed using Pearson's test and a contour plot generated to visualize the effect.
RESULTS
Correlation of allelic score revealed two distinct complexity behaviors in premutation alleles. No significant correlation was observed between the allelic score of premutation alleles and age at amenorrhea. The same lack of significant correlation was observed regarding normal-sized alleles, despite a nearly significant trend.
CONCLUSIONS
Our results suggest that the use of allelic scores combination have the potential to explain female infertility, namely the development of FXPOI, or ovarian dysfunction, despite the lack of correlation with age at amenorrhea. Such a finding is of great clinical significance for early identification of females at risk of ovulatory dysfunction, enhancement of fertility preservation techniques, and increasing the probability for a successful pregnancy in females with premutations. Additional investigation is necessary to validate this hypothesis.
Topics: Humans; Female; Fragile X Mental Retardation Protein; Amenorrhea; Alleles; Primary Ovarian Insufficiency; Adult; Heterozygote; Mutation; Fragile X Syndrome; Age Factors; Young Adult; Adolescent
PubMed: 38907244
DOI: 10.1186/s12958-024-01227-5 -
BMC Geriatrics Jun 2024Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for... (Observational Study)
Observational Study
BACKGROUND
Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for functional disability, but the role of frailty in the association has not been clarified.
METHODS
Forty thousand five hundred sixty-two community-dwelling older adults aged 65 years and over who were insured by public health insurance as of April 2018 were followed up for a median of 3.0 years. Masticatory function was categorized as good, moderate, or poor based on a self-reported questionnaire. The development of functional disability was defined as a new certification of the need for long-term care. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs).
RESULTS
During the follow-up period, 1,397 individuals experienced functional disability. After adjusting for age, sex, comorbidities, medical history, and lifestyle behaviors, the HR for incident functional disability was significantly higher in the moderate and poor groups compared to the good group (moderate, HR 1.21 [95% CI, 1.07-1.37]; poor, HR 1.64 [95% CI, 1.03-2.62]). However, after additional adjustment for frailty-related factors-namely, underweight, regular exercise, and gait speed-the association was attenuated in both the moderate group (HR 1.06 [95% CI, 0.94-1.21]) and the poor group (HR 1.51 [95% CI, 0.94-2.41]).
CONCLUSIONS
Masticatory dysfunction was significantly associated with incident functional disability in a community-dwelling older Japanese population. Our findings suggest that masticatory dysfunction may be a surrogate of frailty rather than a direct cause of functional disability.
Topics: Humans; Aged; Male; Female; Frailty; Mastication; Aged, 80 and over; Independent Living; Frail Elderly; Disabled Persons; Disability Evaluation; Risk Factors; Geriatric Assessment; Japan
PubMed: 38907214
DOI: 10.1186/s12877-024-05131-w -
Scientific Reports Jun 2024Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or...
Hereditary spastic paraplegias are a diverse group of degenerative disorders that are clinically categorized as isolated; with involvement of lower limb spasticity, or symptomatic, where spastic paraplegia is complicated by further neurological features. We sought to identify the underlying genetic causes of these disorders in the participating patients. Three consanguineous families with multiple affected members were identified by visiting special schools in the Punjab Province. DNA was extracted from blood samples of the participants. Exome sequencing was performed for selected patients from the three families, and the data were filtered to identify rare homozygous variants. ExomeDepth was used for the delineation of the copy number variants. All patients had varying degrees of intellectual disabilities, poor speech development, spasticity, a wide-based gait or an inability to walk and hypertonia. In family RDHR07, a homozygous deletion involving multiple exons and introns of SPG11 (NC000015.9:g.44894055_449028del) was found and correlated with the phenotype of the patients who had spasticity and other complex movement disorders, but not those who exhibited ataxic or indeterminate symptoms as well. In families ANMD03 and RDFA06, a nonsense variant, c.985C > T;(p.Arg329Ter) in DDHD2 and a frameshift insertion‒deletion variant of AP4B1, c.965-967delACTinsC;p.(Tyr322SerfsTer14), were identified which were homozygous in the patients while the obligate carriers in the respective pedigrees were heterozygous. All variants were ultra-rare with none, or very few carriers identified in the public databases. The three loss of function variants are likely to cause nonsense-mediated decay of the respective transcripts. Our research adds to the genetic variability associated with the SPG11 and AP4B1 variants and emphasizes the genetic heterogeneity of hereditary spastic paraplegia.
Topics: Humans; Male; Female; DNA Copy Number Variations; Pedigree; Spastic Paraplegia, Hereditary; Exons; Child; Adolescent; Adult; Exome Sequencing; Child, Preschool; Adaptor Protein Complex 4; Consanguinity; Homozygote; Phenotype; Young Adult; Proteins
PubMed: 38906889
DOI: 10.1038/s41598-024-64922-8 -
Translational Psychiatry Jun 2024Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via "trial and error". Given the varied presentation...
Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via "trial and error". Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining data across trials poses numerous challenges. There is also persistent concern that machine learning models can propagate harmful biases. We have created a methodology for organizing and preprocessing depression clinical trial data such that transformed variables harmonized across disparate datasets can be used as input for feature selection. Using Bayesian optimization, we identified an optimal multi-layer dense neural network that used data from 21 clinical and sociodemographic features as input in order to perform differential treatment benefit prediction. With this combined dataset of 5032 individuals and 6 drugs, we created a differential treatment benefit prediction model. Our model generalized well to the held-out test set and produced similar accuracy metrics in the test and validation set with an AUC of 0.7 when predicting binary remission. To address the potential for bias propagation, we used a bias testing performance metric to evaluate the model for harmful biases related to ethnicity, age, or sex. We present a full pipeline from data preprocessing to model validation that was employed to create the first differential treatment benefit prediction model for MDD containing 6 treatment options.
Topics: Humans; Depressive Disorder, Major; Machine Learning; Bayes Theorem; Clinical Trials as Topic; Female; Male; Antidepressive Agents; Adult; Middle Aged; Neural Networks, Computer
PubMed: 38906883
DOI: 10.1038/s41398-024-02970-4 -
Cell Death Discovery Jun 2024Peripheral vascular disease (PVD) is an emerging public health burden with a high rate of disability and mortality. Gasdermin D (GSDMD) has been reported to exert...
Peripheral vascular disease (PVD) is an emerging public health burden with a high rate of disability and mortality. Gasdermin D (GSDMD) has been reported to exert pyroptosis and play a critical role in the pathophysiology of many cardiovascular diseases. We ought to determine the role of GSDMD in the regulation of perfusion recovery after hindlimb ischemia (HLI). Our study revealed that GSDMD-mediated pyroptosis occurred in HLI. GSDMD deletion aggravated perfusion recovery and angiogenesis in vitro and in vivo. However, how GSDMD regulates angiogenesis after ischemic injury remains unclear. We then found that GSDMD-mediated pyroptosis exerted the angiogenic capacity in macrophages rather than endothelial cells after HLI. GSDMD deletion led to a lower level of CCL11 in mice serum. GSDMD knockdown in macrophages downregulated the expression and decreased the releasing level of CCL11. Furthermore, recombinant CCL11 improved endothelial functions and angiogenesis, which was attenuated by CCL11 antibody. Taken together, these results demonstrate that GSDMD promotes angiogenesis by releasing CCL11, thereby improving blood flow perfusion recovery after hindlimb ischemic injury. Therefore, CCL11 may be a novel target for prevention and treatment of vascular ischemic diseases.
PubMed: 38906863
DOI: 10.1038/s41420-023-01764-9 -
Stroke and Vascular Neurology Jun 2024The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.
BACKGROUND
The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.
OBJECTIVE
We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.
METHODS
In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.
RESULTS
The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.
CONCLUSIONS
Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.
PubMed: 38906547
DOI: 10.1136/svn-2023-002962 -
The Journal of Allergy and Clinical... Jun 2024Breathlessness is a disabling symptom, with complexity that is often under recognised and under treated in asthma.
BACKGROUND
Breathlessness is a disabling symptom, with complexity that is often under recognised and under treated in asthma.
OBJECTIVE
To highlight the burden of breathlessness in people with severe compared with mild-to-moderate asthma and identify psychophysiological correlates of breathlessness.
METHODS
This was a cross-sectional study of people with mild-to-severe asthma, who attended two in-person visits to complete a multidimensional assessment. The proportion of people with mild-to-moderate versus severe asthma who reported physically limiting breathlessness (modified Medical Research Council [mMRC] dyspnoea score ≥2) was compared. Psychophysiological factors associated with breathlessness in people with asthma were identified via a directed acyclic graph and explored with multivariate logistic regression to predict breathlessness.
RESULTS
144 participants were included, of which, 74 (51%) had mild-to-moderate asthma and 70 (49%) severe asthma. Participants were predominantly female (n=103, 72%) with a median (quartile 1, quartile 3) age of 63.4 (50.5,69.5) years and body mass index (BMI) of 31.3 (26.2, 36.0) kg/m. The proportion of people reporting mMRC ≥2 was significantly higher in those with severe- (n=37, 53%) compared with mild-to-moderate (n=21, 31%) asthma (p=0.013). Dyspnoea-12 Total (8.00 [4.75, 17.00] versus 5.00 [2.00, 11.00], p=0.037) score was also significantly higher in the severe asthma group. Significant predictors of physically limiting breathlessness were: BMI, asthma control, exercise capacity, and hyperventilation symptoms. Airflow limitation and type-2 inflammation were poor breathlessness predictors.
CONCLUSION
Over half of people with severe asthma experience physically limiting breathlessness despite treatment. Targeting psychophysiological factors, or traits, associated with breathlessness may help relieve this distressing symptom, which is of high priority to people with asthma.
PubMed: 38906398
DOI: 10.1016/j.jaip.2024.06.019